206
methodologies are often not suitable for nanotoxicology assessment due to the possible interferences that occur while common toxicological assays are preformed
(Shatkin and Ong 2016). Therefore, specific adaptations to these assays or alternative ones should be also considered to overcome the limitations of usual and established testing.
In this chapter, we intent to highlight the most relevant aspects to be considered
in nanotoxicological studies, taking as an example DDNCs. Starting with the reference to the main physicochemical parameters that are primarily evaluated, we will
review the different analytical methodologies available for the assessment of NMs
induced toxicity, from the classical tests and evaluation protocols to novel “omics”
techniques, as well as to discuss the challenges to overcome in the future in
this matter.
8.2 Drug Delivery Nanocarriers (DDNCs)
Established drug formulations often exhibit limitations related to pharmacokinetics
and barrier transport, such as poor solubility, permeability, and bioavailability
(Szabo and Zelko 2015). The identified limitations of classical drug therapy have
been mentioned in Fig. 8.1 (Soliman 2017).
The attempt to overcome these problems was one of the most relevant challenge
of pharmaceutical industry in the last years. Apart from this, it was also the reason
of the investigation for nanoparticles based on drug delivery platforms, which can
be a suitable vehicle to overcome the identified limitations (Blanco et al. 2015).
DDNCs have emerged offering new possibilities and profiles for drugs which have
not been explored at their maximum potentiality and/or to re-direct their use in different administration routes.
Engineering of DDNCs with proper physicochemical properties will allow the
combination of different NMs with a high biodegradability and biocompatibility
(Bilia et al. 2014). The main properties of DDNCs have been summarized in
Fig. 8.2. To achieve a therapeutic effect, they must overcome biological barriers
(Bilia et al. 2014).
Besides targeted drug delivery, imaging and diagnosis are also applications influenced by the surface properties of the carriers and have been exploited for (i) early
stage cancer diagnosis (Liu et al. 2007), (ii) assessment of real-time treatment
(Rowland et al. 2012), (iii) high-concentration site-specific drug delivery (Lee and
Wong 2011); (iv) mutations detection (Youns et al. 2011), (v) identification of new
targets for clinical research (Heidel and Davis 2011).
Different types of DDNCs have been developed depending on the type of NMs,
screened and selected according to the properties of the drug to be loaded (Fig. 8.3).
Different DDNCs, with stability related to their functionality, are classified and
characterized according to the chemical nature of the drug carrier. As shown in
Fig. 8.3, polymeric nanoparticles are reservoir-based nanosystems composed of an
inner liquid phase surrounded by a polymeric layer that can control the release,
M. C. Teixeira et al.
methodologies are often not suitable for nanotoxicology assessment due to the possible interferences that occur while common toxicological assays are preformed
(Shatkin and Ong 2016). Therefore, specific adaptations to these assays or alternative ones should be also considered to overcome the limitations of usual and established testing.
In this chapter, we intent to highlight the most relevant aspects to be considered
in nanotoxicological studies, taking as an example DDNCs. Starting with the reference to the main physicochemical parameters that are primarily evaluated, we will
review the different analytical methodologies available for the assessment of NMs
induced toxicity, from the classical tests and evaluation protocols to novel “omics”
techniques, as well as to discuss the challenges to overcome in the future in
this matter.
8.2 Drug Delivery Nanocarriers (DDNCs)
Established drug formulations often exhibit limitations related to pharmacokinetics
and barrier transport, such as poor solubility, permeability, and bioavailability
(Szabo and Zelko 2015). The identified limitations of classical drug therapy have
been mentioned in Fig. 8.1 (Soliman 2017).
The attempt to overcome these problems was one of the most relevant challenge
of pharmaceutical industry in the last years. Apart from this, it was also the reason
of the investigation for nanoparticles based on drug delivery platforms, which can
be a suitable vehicle to overcome the identified limitations (Blanco et al. 2015).
DDNCs have emerged offering new possibilities and profiles for drugs which have
not been explored at their maximum potentiality and/or to re-direct their use in different administration routes.
Engineering of DDNCs with proper physicochemical properties will allow the
combination of different NMs with a high biodegradability and biocompatibility
(Bilia et al. 2014). The main properties of DDNCs have been summarized in
Fig. 8.2. To achieve a therapeutic effect, they must overcome biological barriers
(Bilia et al. 2014).
Besides targeted drug delivery, imaging and diagnosis are also applications influenced by the surface properties of the carriers and have been exploited for (i) early
stage cancer diagnosis (Liu et al. 2007), (ii) assessment of real-time treatment
(Rowland et al. 2012), (iii) high-concentration site-specific drug delivery (Lee and
Wong 2011); (iv) mutations detection (Youns et al. 2011), (v) identification of new
targets for clinical research (Heidel and Davis 2011).
Different types of DDNCs have been developed depending on the type of NMs,
screened and selected according to the properties of the drug to be loaded (Fig. 8.3).
Different DDNCs, with stability related to their functionality, are classified and
characterized according to the chemical nature of the drug carrier. As shown in
Fig. 8.3, polymeric nanoparticles are reservoir-based nanosystems composed of an
inner liquid phase surrounded by a polymeric layer that can control the release,
M. C. Teixeira et al.